Grant Details
Grant Number: |
2U24CA258118-05 Interpret this number |
Primary Investigator: |
Godley, Lucy |
Organization: |
Northwestern University At Chicago |
Project Title: |
Myeloid Malignancy Variant Curation Expert Panel |
Fiscal Year: |
2024 |
Abstract
Project Summary
Germline predisposition to hematopoietic malignancies is more common than previously appreciated and is best
understood for the myeloid malignancies. Variants in genes such as RUNX1, DDX41, GATA2, ANKRD26, ETV6,
CEBPA, SAMD9/SAMD9L, and TERT/TERC are among those commonly identified in patients. Recognizing the
importance of germline predisposition to myeloid malignancies, all of the recently-updated classification schema
include this entity among their diagnostic criteria. The American Society of Hematology and ClinGen first
partnered in 2017 to support the Myeloid Malignancy Variant Curation Expert Panel (MM-VCEP), which was
funded subsequently by the NIH U24 mechanism. In its initial funding period, the MM-VCEP has:organized a
diverse biocurator network consisting of a Lead Biocurator and 16 biocurators; developed, implemented, and
revised RUNX1 variant curation rules that are now in use throughout the world; completed the first international
As a highly motivated and
productive group, the MM-VCEP seeks continued support for curation of RUNX1, DDX41, and GATA2 variants
and development of curation rules for additional genes that confer risk for myeloid malignancies, including
ANKRD26, ETV6, CEBPA, SAMD9/SAMD9L, and TERT/TERC. The MM-VCEP seeks to use segregation codes
at the strongest level possible and will develop novel collaborations with patient/family-focused organizations,
including ConnectMyVariant, the RUNX1 Research Program, and Team Telomere, Inc., to do so. Additional
variant collections that have deep phenotype and provider contact information, such as the St. Jude Children’s
Research Hospital SAMD9/SAMD9L database and the Clinical Care Consortium for Telomere-Associated
Ailment international registry, will be incorporated as well. Thus, the MM-VCEP seeks to continue its important
work in providing worldwide standards for consistent variant curation so that patients at risk of developing myeloid
malignancies can receive optimal clinical care and appropriate surveillance strategies for cancer detection and
organ dysfunction.
GATA2 Phenotype Survey; and developed pilot curation rules for DDX41 and GATA2.
Publications
Insights into the Molecular Mechanisms of Genetic Predisposition to Hematopoietic Malignancies: The Importance of Gene-Environment Interactions.
Authors: Cobaleda C.
, Godley L.A.
, Nichols K.E.
, Wlodarski M.W.
, Sanchez-Garcia I.
.
Source: Cancer discovery, 2024-03-01; 14(3), p. 396-405.
PMID: 38426560
Related Citations
Revision of RUNX1 variant curation rules.
Authors: Feurstein S.
, Luo X.
, Shah M.
, Walker T.
, Mehta N.
, Wu D.
, Godley L.A.
.
Source: Blood advances, 2022-08-23; 6(16), p. 4726-4730.
PMID: 35764482
Related Citations
Germline variants drive myelodysplastic syndrome in young adults.
Authors: Feurstein S.
, Churpek J.E.
, Walsh T.
, Keel S.
, Hakkarainen M.
, Schroeder T.
, Germing U.
, Geyh S.
, Heuser M.
, Thol F.
, et al.
.
Source: Leukemia, 2021 Aug; 35(8), p. 2439-2444.
EPub date: 2021-01-28.
PMID: 33510405
Related Citations